Journal
NEURAL REGENERATION RESEARCH
Volume 12, Issue 4, Pages 538-548Publisher
WOLTERS KLUWER MEDKNOW PUBLICATIONS
DOI: 10.4103/1673-5374.205083
Keywords
amyloid beta (A beta); retinal neurons; retina; mouse models; age related macular degeneration (AMD)
Categories
Funding
- National Centre for the Replacement Refinement & Reduction of Animals in Research (NC3R) [NC/L001152/1]
- Macular Society, UK
- National Eye Research Centre
- Gift of Sight Appeal
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [NC/L001152/1] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0515-10020] Funding Source: researchfish
- Sight Research UK [SAC 020] Funding Source: researchfish
Ask authors/readers for more resources
Age-related macular degeneration (AMD) causes irreversible loss of central vision for which there is no effective treatment. Incipient pathology is thought to occur in the retina for many years before AMD manifests from midlife onwards to affect a large proportion of the elderly. Although genetic as well as non-genetic/environmental risks are recognized, its complex aetiology makes it difficult to identify susceptibility, or indeed what type of AMD develops or how quickly it progresses in different individuals. Here we summarize the literature describing how the Alzheimer's-linked amyloid beta (A) group of misfolding proteins accumulate in the retina. The discovery of this key driver of Alzheimer's disease in the senescent retina was unexpected and surprising, enabling an altogether different perspective of AMD. We argue that A fundamentally differs from other substances which accumulate in the ageing retina, and discuss our latest findings from a mouse model in which physiological amounts of A were subretinally-injected to recapitulate salient features of early AMD within a short period. Our discoveries as well as those of others suggest the pattern of A accumulation and pathology in donor aged/AMD tissues are closely reproduced in mice, including late-stage AMD phenotypes, which makes them highly attractive to study dynamic aspects of A-mediated retinopathy. Furthermore, we discuss our findings revealing how A behaves at single-cell resolution, and consider the long-term implications for neuroretinal function. We propose A as a key element in switching to a diseased retinal phenotype, which is now being used as a biomarker for late-stage AMD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available